A case of respiratory syncytial virus-associated encephalopathy in which the virus was detected in cerebrospinal fluid and intratracheal aspiration despite negative rapid test results.

We report a first case of respiratory syncytial virus (RSV) infection-associated encephalopathy in which RS virus was detected in the patient's intratracheal aspiration and cerebrospinal fluid despite negative rapid test results of the nasal swab. The patient's findings and clinical course coincided with those of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) with severe subsequent sequelae. Our case indicates that clinicians should consider RSV infection when patients have AESD with unknown etiology.

Examination of neurological prognostic markers in patients with respiratory syncytial virus-associated encephalopathy.

No biomarker has been established as a prognostic indicator of acute encephalopathy associated with various etiological factors. In this study, we examined useful prognostic biomarkers in patients with acute encephalopathy associated with respiratory syncytial virus (RSV) infection. The subjects were 11 children with RSV-associated encephalopathy admitted to our hospital. We measured the levels of interleukin (IL)-6, brain-derived neurotrophic factor (BDNF) and nitrogen oxide (NO)x in cerebrospinal fluid collected on the day of admission. Using the pediatric cerebral performance categories (PCPC) score as a prognostic indicator, we evaluated the association between the biomarkers and neurologic prognosis. Concerning neurologic prognosis, sequelae were noted in more than 50% of the subjects. There was no association between prognosis and age/sex. Increases in the levels of all biomarkers were observed in all subjects. IL-6 and BDNF levels were correlated with PCPC score, but not with NOx. Of the biomarkers investigated, the IL-6 and BDNF levels in cerebrospinal fluid were shown to be correlated with neurologic prognosis. Because many patients with this disease had severe sequelae, assessment should be conducted by early evaluation of the biomarkers examined in this study with respect to the clinical course.

MicroRNA Profiling from RSV-Infected Biofluids, Whole Blood, and Tissue Samples.

Several studies have shown that respiratory syncytial virus (RSV) can modulate the host innate immune response by dysregulation of host microRNAs (miRNAs) related to the antiviral response, a feature that also affects the memory immune response to RSV (Thornburg et al. MBio 3(6), 2012). miRNAs are small, endogenous, noncoding RNAs that function in posttranscriptional gene regulation. Here, we explain a compilation of methods for the purification, quantification, and characterization of miRNA expression profiles in biofluids, whole blood samples, and tissue samples obtained from in vivo studies. In addition, this chapter describes methods for the isolation of exosomal miRNA populations. Understanding alterations in miRNA expression profiles and identifying miRNA targets genes, and their contribution to the pathogenesis of RSV, may help elucidate novel mechanism of host-virus interaction (Rossi et al., Pediatr Pulmonol, 2015).

Apnea induced by respiratory syncytial virus infection is not associated with viral invasion of the central nervous system.

We aimed to study whether direct central nervous system invasion is responsible for the neurologic manifestations seen in hospitalized infants with respiratory syncytial virus (RSV) infection. Cerebrospinal fluid from infants with RSV infection was tested for the detection of the following respiratory RNA viruses: RSV, influenza A and B, pandemic influenza H1N1, Parainfluenza-3, human metapneumovirus, adenovirus, parechovirus and enterovirus. All children tested negative for the presence of viral material in the cerebrospinal fluid. Our results support the notion that the mechanism of RSV-induced neurologic manifestations, including apnea, is not direct central nervous system invasion.

Production of chemokines in respiratory syncytial virus infection with central nervous system manifestations.

Respiratory syncytial virus (RSV) infection in children can be associated with acute encephalopathy. However, the roles of cytokines in the cerebrospinal fluid (CSF) of such patients remain unevaluated. In this study, a profile of 17 cytokines was determined for eight RSV-infected children with neurological complications. In one patient with high levels of 13 cytokines, a cytokine storm was considered to have occurred. Interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1ß levels were also high in other patients. These data suggest that chemokines in CSF play roles in neurological complications in RSV-infected children.

Classification of acute encephalopathy in respiratory syncytial virus infection.

Infection with respiratory syncytial virus (RSV) is known to be associated with central nervous system symptoms such as convulsions. We investigated cytokines, nitrogen oxide (NO)( x ), and the viral genome in cerebrospinal fluid (CSF) obtained from children with RSV infection-related convulsions or central nervous symptoms and compared the data with type of encephalopathy. Of nine patients enrolled (six boys and three girls; aged 10 days-3 years), one metabolic error, five excitotoxicity, one cytokine storm, and two hypoxia cases were found. The patients presented with unilateral convulsions, generalized convulsions, and convulsions following cardiopulmonary arrest, apnea, and nuchal rigidity. In all patients, a rapid check for RSV of nasal fluid was positive. The RSV genome (subgroup A) was detected in the CSF of five of the nine patients; two patients with hypoxic encephalopathy were negative for the RSV genome. The CSF interleukin (IL)-6 levels were high only in patients with the excitotoxicity and cytokine storm type of encephalopathy. NO( x ) levels were high in all the subject cases. In the excitotoxicity type, NO( x ) levels were significantly higher than those in the control and other groups. NO( x ) level may become an important parameter for the diagnosis and classification of acute encephalopathy in RSV. Strategies to treat each type of encephalopathy, targeting cytokines and free radicals, should be established.

Cerebrospinal fluid analysis in children with seizures from respiratory syncytial virus infection.

We report 3 cases of respiratory syncytial virus infection-associated seizures; their abnormalities of cerebrospinal fluid (increased interleukin-6 and positive for virus by highly sensitive assay) were documented. These data revealed that neurological involvement might be caused by a direct invasion.

Elevated CSF IL-6 in a patient with respiratory syncytial virus encephalopathy.

The patient was an 11-month-old boy who developed encephalopathy associated with respiratory syncytial virus bronchiolitis. Right hemispheric encephalopathy was indicated by left hemiparesis and a diffuse right hemispheric lesion detected with magnetic resonance imaging. Elevated levels of interleukin-6 in the cerebrospinal fluid during the acute phase suggested the involvement of increased production of one or more cytokines in the pathogenesis of viral related encephalopathy, similarly to that proposed for influenza encephalopathy.